West Coast Editor

Genzyme Corp.'s success in its Phase III trial with Mozobil (plerixafor) in multiple myeloma laid to rest any investors' jitters that might have lingered in the wake of the win two weeks ago in non-Hodgkin's lymphoma, and the company plans to file for approval in both indications, here and overseas, during the first half of next year.

Henri Termeer, president and CEO of Cambridge, Mass.-based Genzyme, called the results "exceptionally strong confirmation that we are on to something here" during a conference call with investors, though Wall Street seemed to take the news in stride. Genzyme's stock (NASDAQ:GENZ) rose $1.10 Thursday to close at $64.53.

Mozobil, also known as AMD3100, is an antagonist of the SDF-1/CXCR4 complex, designed to boost the number of stem cells collected before a stem cell transplant. Unlike the standard of care, which is granulocyte-colony stimulating factor (G-CSF), Mozobil acts to release stem cells from the bone marrow so they can circulate.

The trial included 302 patients undergoing a hematopoietic stem cell (HSC) transplant for multiple myeloma at medical centers in the U.S., Canada and Europe. Like the NHL trial, the MM study tested Mozobil's ability to increase HSCs collected for a transplant. Researchers compared the stem cell yield from patients treated with Mozobil following G-CSF to the yield from patients given placebo after G-CSF.

In the primary efficacy endpoint, 72 percent of patients treated with Mozobil and G-CSF achieved the target threshold for collection of at least 6 million CD34+cells/kg from the peripheral blood with two days or fewer of apheresis sessions, compared with 34 percent of patients in the G-CSF/placebo group. The twofold increase was statistically significant in favor of the Mozobil-treated patients (p<0.0001).

Like the previous trial, the results exceeded the 20 percent absolute difference that was prospectively defined as a successful result by the FDA's special protocol assessment.

The median number of days to achieve the target of 6 million cells was one day for the Mozobil/G-CSF group and four days for the G-CSF/placebo group. More than half of patients treated with Mozobil and G-CSF reached the target cells in the first day of apheresis. By comparison, it took four days for a similar percentage of the G-CSF/placebo group to reach the same level.

Mark Goldberg, senior vice president for clinical research at Genzyme, pointed to the reduction in apheresis sessions as a way of improving quality of life for patients, with fewer days of G-CSF and no chemotherapy - all of which allows major transplant centers to "plan much better and utilize their time and their very valuable chairs and beds much more efficiently." The latest trial recorded just one serious adverse event, showing up in the G-CSF arm. "We're really not concerned at all about any serious toxicities," Goldberg said. "The only things we saw were some mild to moderate, usually mild, diarrhea and nausea, and at the injection site, a little bit of redness." He called Mozobil "incredibly safe."

Termeer would not discuss pricing, but did not dispute an analyst's guess that the low cost of goods could mean a profit margin "north of 90 percent" for Mozobil. "There's a tremendous amount of leverage in the Genzyme picture right now, and this adds to it," he said, but the company will be exploring Mozobil in other indications, including chemo sensitization. Three studies are starting up shortly, with one already under way and two more set to begin in September and October. Two more trials are slated for the first half of next year.

Although some analysts have been less optimistic, Genzyme estimates peak annual revenue from Mozobil at $400 million. The company acquired the drug in its buyout of AnorMED Inc., of Vancouver, British Columbia, outbidding Cambridge, Mass.-based Millennium Pharmaceuticals Inc., and paying $13.50 per outstanding share, or about $580 million in cash, after Millennium declined to increase its $12 per share offer. (See BioWorld Today, Oct. 18, 2006.)

"You will hear about Mozobil a great deal more," Termeer said.